Quorum Sensing and NF-κB Inhibition of Synthetic Coumaperine Derivatives from Piper nigrum.

Bacterial communication, termed Quorum Sensing (QS), is a promising target for virulence attenuation and the treatment of bacterial infections. Infections cause inflammation, a process regulated by a number of cellular factors, including the transcription Nuclear Factor kappa B (NF-κB); this factor is found to be upregulated in many inflammatory diseases, including those induced by bacterial infection. In this study, we tested 32 synthetic derivatives of coumaperine (CP), a known natural compound found in pepper (Piper nigrum), for Quorum Sensing Inhibition (QSI) and NF-κB inhibitory activities. Of the compounds tested, seven were found to have high QSI activity, three inhibited bacterial growth and five inhibited NF-κB. In addition, some of the CP compounds were active in more than one test. For example, compounds CP-286, CP-215 and CP-158 were not cytotoxic, inhibited NF-κB activation and QS but did not show antibacterial activity. CP-154 inhibited QS, decreased NF-κB activation and inhibited bacterial growth. Our results indicate that these synthetic molecules may provide a basis for further development of novel therapeutic agents against bacterial infections.

3,3'-Diindolylmethane (DIM): A Potential Therapeutic Agent against Cariogenic Streptococcus mutans Biofilm.

Indole, a metabolite of the amino acid tryptophan, has been proven to act as a signal molecule in bacteria, acting in different aspects of biofilm formation. The oral biofilm is a type of biofilm that has consequences for human health. It is a complex, three-dimensional structure that develops on the surface of teeth via the attachment of primary microbial colonizers. Many oral infections are caused by an imbalance occurring in the microorganisms naturally found in oral biofilms and are considered major public health concerns. In this study, we test the effect of a natural bis-indole, 3,3'-Diindolylmethane (DIM), in mitigating the pathogenicity of the oral biofilm inhabiting bacterium Streptococcus mutans, a bacterium that is considered to be a principal etiological agent in dental caries. Our study found that DIM was able to attenuate S. mutans biofilm formation by 92%. Additionally, treatment with DIM lowered extracellular polymeric substance (EPS) production and decreased its durability significantly under acidic conditions. Therefore, the anti-biofilm and anti-virulence properties of DIM against S. mutans bacteria in an "oral setting" provides evidence for its usefulness in reducing biofilm formation and potentially for caries attenuation.

The association between physical pain and cannabis use in daily life: An experience sampling method.

BACKGROUND: Previous research shows that between individuals there is a positive association between medically motivated use and cannabis use frequency and quantity. While between-subjects' analyses are useful for understanding shared vulnerabilities, research has so far not examined within-subjects' relationships which are closer to evaluating functional relationships (i.e., do individuals tend to use cannabis more heavily subsequent to elevations in pain experiences?). To better understand the association between experiences of pain and cannabis use, the current paper examines whether there is a functional within-subjects association between experiences of pain and heavy cannabis use. METHODS: 182 regular cannabis users without a medical cannabis license were asked to report momentary experiences of physical pain, whether they had used cannabis, and if so, quantity consumed five times per day over a five-day period on their smartphones. Mixed effects models examined the relations between within- and between-subjects experiences of pain and cannabis use and quantity consumed. RESULTS: Elevated experiences of pain were not associated with cannabis use occasions at the within- or between-subjects level. Experiences of pain were associated with greater amount of cannabis consumed at the within-subjects level, but not at the between-subjects level. CONCLUSIONS: Experiences of pain are not associated with decisions about whether or not to use cannabis. Once cannabis users are in cannabis-using situations, they tend to use larger amounts when they are experiencing elevated levels of pain. This may have implications for cannabis abuse treatment as pain may make it more difficult for users to reduce their consumption.